Seeing Further

by Bill Bryson

  Tiny, courageous and independent, Lonsdale dealt with glass ceilings by refusing to see them, and achieved a series of notable firsts for British women in science. In 1945 she and Marjorie Stephenson, the Cambridge biochemist, signed the Register of Fellows of the Royal Society, the first women to do so since its foundation in 1660. Their election followed delicate political manoeuvring largely on the part of the then President, Sir Henry Dale (who became Lonsdale’s boss at the RI after William Bragg’s death in 1942) to overturn what prejudice remained among the Fellowship after legal obstacles were removed in 1919. She also benefited from the energetic advocacy of her erstwhile fellow graduate student, Bill Astbury. It was his presentation of a correctly drawn up certificate of her candidacy that prompted Dale to win the majority of the Fellowship over to this revolutionary move.5

  In 1949 Lonsdale became the first woman to be appointed to a professorship at University College London, and in 1968 the first to become President of the British Association for the Advancement of Science. A Quaker and conscientious objector, in 1943 she refused to pay the fine of £2 for nonregistration for civil defence work, an action that earned her a month in Holloway prison. Appalled at the monotony of prison life, she became an active supporter of prison reform after her release. At the height of the Cold War she wrote a book, Is Peace Possible?,6 giving a personal response to her ‘sense of corporate guilt and responsibility that scientific knowledge should have been so misused’ as to develop atomic weapons. Her example was an inspiration to the generations of women crystallographers who followed.

  Also born in Ireland, to a comfortably-off farming family, John Desmond Bernal7 had astonished his Cambridge tutors as an undergraduate by producing unbidden an eighty-page manuscript giving mathematical derivations of the 230 ‘space groups’ of classical crystallography. The diversion of his efforts probably cost him a First, but left them in no doubt of his quick grasp of theoretical concepts, and like Astbury he came to Bragg with their enthusiastic recommendation. Though he never completed a PhD thesis, during his time at the RI he solved the structures of single crystals, notably graphite, designed the X-ray goniometer that all crystallographers used to mount and photograph their crystals for years afterwards, and made further theoretical contributions to the subject. In 1927 he returned to Cambridge as the first Lecturer in Structural Crystallography in the department of mineralogy.

  THE SAGE OF SCIENCE

  Bernal was a polymath, able to discourse convincingly and at length on any topic from Chinese art to quantum physics. While still an undergraduate he had earned the nickname ‘Sage’ from his fellow students: the name stuck throughout his life, used by all his friends and colleagues with barely a trace of irony. Nor were his energies confined to intellectual pursuits. Exchanging devout Roman Catholicism for equally devout Marxism as an undergraduate, he became a leading member of the ‘visible college’ of scientists and socialists who came to prominence in the 1930s.8 Always linking thought to action, he was an indefatigable organiser, notably of the Association of Scientific Workers and later its international counterpart, the World Federation of Scientific Workers. His desire for experimentation extended far outside the laboratory: he pursued a private life of unabashed promiscuity, justified to himself and others by his political mission to escape the restrictions of social convention.

  Bernal was unusual among scientists in the degree to which he reflected on his experiences and beliefs in both public and private. In his early life he kept diaries charting everything from his scientific and political insights to his sexual conquests, and at the age of only twenty-five began a passionate and idealistic memoir (never published) entitled Microcosm. Soon afterwards he produced his first published book, The World, the Flesh and the Devil: An Enquiry into the Future of the Three Enemies of the Rational Soul (1929), which accurately predicted a number of scientific developments including the Apollo space programme, and just as inaccurately forecast the triumph of world Communism. A later and much more influential book, The Social Function of Science (1939), argued for central planning of science on the Soviet model, with the goal of improving human welfare rather than pursuing knowledge for its own sake.

  The Second World War gave Bernal the opportunity to put his own science to the service of society. He was involved in studies of the accuracy of bombing raids and their effects, which influenced both civil defence policy and Bomber Command, and conducted surveys of the Normandy coastline and seabed as part of the preparation for the D-day landings. After the war he aligned himself, like many of his fellow scientists, with opposition to nuclear warfare, coining the phrase ‘weapons of mass destruction’ at a speech to the British-Soviet Society in London in 1949. His influence might have been greater had it not been for his blindly uncritical support for Soviet Communism, which was unwavering in the face of Stalin’s purges, the Lysenko affair and the invasion of Hungary. His accusation that the direction of Western science was dictated by warmongers led to his removal from the Council of the British Association for the Advancement of Science. Despite his valuable service during the war years, he never received any honours in Britain.

  The double Nobel Prize-winner Linus Pauling (For.Mem.RS 1949) is one of many who described Bernal as the most brilliant scientist they had ever met. Yet he never personally made the kind of breakthrough that would have set him on the road to Stockholm. With so much to do, and so little time, he rarely pursued a scientific project to its conclusion. Instead, he gathered around him a group of able disciples of both sexes and showered them with ideas. They did not let him down.

  PROTEINS AND PRIZES

  Dorothy Crowfoot (later Hodgkin9) was a slim, soft-spoken, first-class graduate in chemistry from Oxford who came to Bernal’s lab in 1932 to begin a PhD. The eldest of four girls, Crowfoot came from a middle-class family who did not see intellectual pursuits as off-limits for women. Her father was a colonial administrator and archaeologist, and her mother, without any formal higher education, became a world expert in ancient textiles. It was she who encouraged Crowfoot’s schoolgirl interest in chemistry by giving her W.H. Bragg’s collected lectures to read, and his account of crystallography captured her imagination.

  Crowfoot excelled in all the practical aspects of crystallography – growing the crystals, mounting them and photographing them – but also had a remarkable ability to visualise the three-dimensional manipulations that the early, trial-and-error stage of the subject demanded. She quickly became Bernal’s right hand, conducting preliminary observations on the dozens of crystals that poured into his lab from all over the world. Asked later how she succeeded so early, she modestly replied that there was so much gold lying about, one could not help picking it up.10

  One day Glenn Millikan, a young scientist and friend of Bernal’s, returned to Cambridge from Sweden with a tube of crystals of the digestive enzyme pepsin in his pocket. Like all enzymes pepsin is a protein, one of a class of biological molecules that are the precision tools of the living body. Enzymes are highly specific catalysts that speed the construction and destruction of all the body’s constituents; other proteins include keratin and collagen that build strong structures such as hair and skin, antibodies that protect us against disease, and hormones such as insulin. All proteins depend for their function on their molecular structure. With care they can be purified and crystallised just like simple salts (though the crystals tend to be very small). The fact that they crystallise at all implies that their molecules have a regular structure – something that not all chemists believed at the time – and Bernal was convinced that solving these structures would reveal the ‘secret of life’.

  When he took the pepsin crystals out of the liquid in the tube he found that they quickly lost their crystalline form, so he mounted a crystal with some of the liquid inside a fine glass capillary before putting it in the X-ray beam. He obtained a pattern of spots, the first time anyone had successfully made a single protein crystal diffract. Crowfoot went on to take a further series of photogra
phs of the crystal until they had enough for a letter to Nature,11 describing their preliminary observations. Protein molecules are so large, consisting of thousands of atoms arranged in folded chains, that the relationship between their X-ray reflections and atomic positions is far from straightforward. Trial-and-error methods could not begin to narrow down the range of possible structures that would produce such patterns. Nevertheless, the Bernal and Crowfoot paper heralded the modern era of protein structure analysis.

  Already at the forefront of the field at the age of twenty-four, in 1934 Crowfoot returned to Oxford where Somerville College (a women-only college) had given her a fellowship, and embarked on an X-ray study of the protein hormone insulin.12 She married the historian Thomas Hodgkin, and despite his long absences promoting adult education in the north of England, had given birth to two children by the end of 1941. A supportive college, indulgent in-laws and cheap domestic labour enabled her to keep working with only the briefest of intervals, despite a severe attack of acute rheumatoid arthritis after the birth of her first child. During the Second World War she was recruited to the secret penicillin project, trying to solve the structure of the miraculously effective antibiotic that had been purified from mould by Howard Florey and his colleagues in Oxford’s Dunn School of Pathology. Penicillin molecules had only a couple of dozen atoms, but the substance proved difficult to crystallise.

  Success followed in 1945 after Kathleen Lonsdale personally brought Hodgkin samples of a more easily crystallisable penicillin derivative from America, where efforts to start industrial production were under way. Hodgkin’s structure unequivocally confirmed the presence of a previously unseen ring of atoms in the molecule, known as a beta lactam ring, that was fundamental to the drug’s ability to incapacitate bacteria. Although this discovery did not immediately lead to the creation of synthetic antibiotics as the project’s industrial partners had hoped, it was one of the first examples of a drug’s function being explained in terms of its structure, a principle that underlies all drug discovery programmes today. Lonsdale was delighted, and hoped for the opportunity to exercise her brand-new status as a Royal Society Fellow on Hodgkin’s behalf:

  I am going to ask a favour; when this work is published, may I communicate it [to the Proceedings of the Royal Society]? If … it is possible I think that it would be rather pleasant that a woman Fellow should communicate such a very important paper by another woman, and I would be very proud to do it.13

  As she had so fervently wished, Hodgkin was herself elected to the Royal Society two years later, aged only thirty-six and by then a mother of three. She went on to solve the structure of the anti-pernicious anaemia factor, Vitamin B12, and in 1960 the Society appointed her its first Wolfson Research Professor. Bernal’s prophecy came true when she was awarded the 1964 Nobel Prize for Chemistry, the first (and so far the only) British woman to win a science Nobel. The following year she was appointed to the Order of Merit, the first woman to receive the honour since Florence Nightingale.

  While Hodgkin developed Bernal’s project in Oxford, another of his students kept it going in Cambridge after Bernal himself had departed for the chair in physics at Birkbeck in 1937. Max Perutz (FRS 1954)14came to Cambridge as a wealthy foreign research student, funded by an allowance from his father who ran a textile business in Vienna. He began work on the protein haemoglobin, the pigment in red blood cells that carries oxygen round the body. But with the Anschluss in 1938 his Jewish family lost everything and had to flee for their lives. His parents eventually arrived in Cambridge and became dependent on his support. Fortunately his excellent X-ray photographs of haemoglobin crystals so impressed the new Cavendish Professor of Physics – none other than Bragg junior, soon to be Sir Lawrence to distinguish him from his father – that he found himself taken on in 1939 as Bragg’s research assistant with a grant from the Rockefeller Foundation.

  As an ‘enemy alien’, Perutz suffered internment in 1940–41, but on his return was recruited (thanks to Bernal, and to a brief pre-war foray into glaciology) to one of the most audacious scientific projects of the war. Project Habbakuk,15 misspelled and misguided, aimed to build a huge fleet of aircraft carriers out of ice to enable planes to refuel as they crossed the Atlantic. Perutz carried out successful experiments on making ice stronger, but the project ran for months before its American partners calculated that construction of the vessels would be hopelessly costly and impractical, and cancelled it. For Perutz, however, its value was incalculable: through it he gained a British passport and the security he had lacked for so long.

  More successful wartime scientific projects, such as penicillin, code-breaking and radar, led the government to increase budgets for peacetime research. Perutz’s work on haemoglobin, championed by Bragg, seemed sufficiently promising for the Medical Research Council to fund a unit on the Molecular Structure of Biological Systems (later called simply Molecular Biology) in the Cavendish Laboratory, under Perutz’s leadership. The crowded but exceptionally well-equipped unit’s mix of physics, chemistry, biology and mathematics proved a magnet for curious minds, especially physicists who had become disillusioned with their subject after Hiroshima.

  Francis Crick (FRS 1959) was one of these, joining Perutz’s unit in 1949 and contributing a new mathematical rigour to his studies of proteins. The restless young American geneticist James Watson (For.Mem.RS 1981) arrived two years later. Informed by fibre diffraction photographs by Maurice Wilkins (FRS 1959) and Rosalind Franklin at King’s College London, the two of them discovered the double helix structure of DNA in 1953.16 The structure was the most important discovery of twentieth-century biology, providing a mechanism that could unite Charles Darwin’s theory of evolution and Gregor Mendel’s model of heredity. A ‘spiral staircase’ of two linked chains of complementary pairs of the four nucleotide bases adenine, thymine, guanine and cytosine, it immediately revealed how such a chemically simple molecule could account for life in all its abundant diversity. ‘It has not escaped our notice’, famously wrote the authors of their classic paper in Nature,17 ‘that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.’ Each chain could make a new double helix, enabling cells and organisms to replicate themselves. Crick and Watson also realised that the infinite number of ‘words’ that could be written in the four-letter alphabet A, T, G and C provided a genetic code to direct the construction of protein chains, though it took the efforts of many scientists until the mid-1960s to crack the code. The discovery ushered in the modern era of biotechnology, in which scientists not only read but edit genetic information to produce animals, plants, medicines or industrial processes tailored to human demands.

  Perutz himself and his colleague John Kendrew (FRS 1960) continued with the much more difficult problem of protein structure. In 1953 Perutz discovered that introducing mercury atoms into the haemoglobin molecule could remove ambiguities in the results obtained from such large, irregular molecules. Combining this technique with pioneering computer analysis, Kendrew solved the structure of myoglobin, an oxygen-carrying protein a quarter of the size of haemoglobin, in 1957. Two years later Perutz and his team finally succeeded with haemoglobin. For the first time it was possible to see how the protein chain encoded by a DNA sequence folded itself into a characteristic, compact shape, as specific to its purpose as the nuts, bolts, valves, pistons, sparkplugs and gearwheels of a motor car. Perutz continued to work on haemoglobin for the rest of his life, describing the mechanism by which the ‘breathing molecule’ seizes and releases oxygen, exploring the evolutionary relationships between haemoglobins of different species, and linking abnormal haemoglobin to disease. Today’s structural biologists use essentially the same technique, though with much better X-ray sources and computer analysis, to explore the whole toolbox of molecular machines that make up the living body. These include the enzyme DNA polymerase that builds new DNA chains on the template of a single DNA strand, and the bacterial flagellar motor, a protein com
plex that rotates the tiny flails that propel bacteria through their fluid worlds.

  In 1962 Perutz and Kendrew shared the Nobel Prize for Chemistry, while Crick, Watson and Wilkins received the accolade for Physiology: an extraordinary sweep for one country, let alone a single laboratory. Sir Lawrence Bragg had been instrumental in forwarding all their claims: he heard of the awards while recovering in hospital from an operation for prostate cancer, leading his doctor to tell his wife that he was ‘over the worst, but now I think he may die of excitement’.18 He had left Cambridge in 1953 to take up his father’s old job as Director of the Royal Institution. Having failed in his first plan of moving Perutz and Kendrew to the RI with him, Bragg started his own protein structure group there. It included David Phillips (FRS 1967), a young post-doctoral researcher from Cardiff, who led a team that solved the next protein structure, the enzyme lysozyme,19 in 1965. With his student Louise Johnson (FRS 1990), he was the first to shed light on the molecular interactions that give enzymes their catalytic effect, without which the chemical reactions that power our lives would be impossible.

  LEGACIES

  Bragg dedicated his last years to restoring the RI, which had gone through a fallow period, to the glory days of Faraday or indeed his own father. Apart from sorting out its finances and establishing a first-class programme of research, he devoted most of his own energies to promoting science literacy. With enormous enjoyment and a knack for the felicitous analogy, he launched a year-round programme of lectures for schools, accompanied by the most spectacular demonstrations his inventive mind could conjure. Not a man for political activism, he took every opportunity through lecturing and broadcasting to present his vision of science as a benign, humanising activity that transcended class, gender and national boundaries. The RI continues this work today.